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Vulvodynia: A Common and Under-Recognized Pain Disorder in Women and Female Adolescents -- Integrating Current Knowledge into Clinical Practice

In cooperation with faculty members Drs. Jacob Bornstein, Andrew Goldstein, Ruby Nguyen, Colleen Stockdale, and Pamela Morrison Wiles, the National Vulvodynia Association revised this program, which is jointly sponsored by Dannemiller, to promote accurate diagnosis and improve patient care.

Cover illustration, by Marit Lindqvist, from Dr. Bohm-Starke’s 2001 thesis, VVS:  Pathology of the Vestibular Mucosa,  included with permission.

© 2016 National Vulvodynia Association

 

 

What we now refer to as “Vulvodynia” was first documented in medical texts in 1880, although some believe that the condition may have been described as far back as the 1st century (McElhiney 2006). Vulvodynia was again described as “supersensitiveness of the vulva” and “a fruitful source of dyspareunia,” before mention of the condition disappeared from medical texts for five decades.

  

 

 

 

 

 

Studies of women found that the incidence of symptom onset is highest between the ages of 18 and 25. Once thought to affect primarily Caucasian women, recent studies indicate that Hispanic women are significantly more likely to develop vulvodynia, and may present with different vulvar pain subtypes. Because vulvodynia is rarely covered in medical school curricula and residency programs, symptoms mimic those of common vulvovaginal infections, and in many cases, no abnormalities of the vulvar tissue can be seen upon examination, women are often misdiagnosed. In 2003, the first federally funded population-based epidemiologic study in Boston found that almost 60 percent of patients reported visiting three or more health care providers to receive a diagnosis, 40 percent of whom remained undiagnosed after three consultations.

Using prevalence estimates of three to seven percent, Xie and colleagues demonstrated the significant economic impact of vulvodynia in the U.S. of $31 to $72 billion in direct and indirect costs.

 

  

This slide summarizes common themes experienced by women with vulvodynia and their interrelation (Donaldson 2010). Living with vulvodynia often limits certain activities of daily living, such as sitting for extended periods, and engaging in sexual intercourse and physical exercise. In severe cases,  women have to resign from their jobs and apply for disability. Several studies summarize the negative biopsychosocial outcomes, personal distress and sexual dysfunction reported by vulvodynia sufferers. Xie found that women with vulvodynia report lower quality of life scores than kidney transplant recipients and those with prior osteoporosis-related fractures (Xie 2012).  Newly diagnosed women report substantial impact of vulvar pain on their lives, and little control over their symptoms (Piper 2012).  Among women of reproductive age, Johnson found that barriers to consistent health care frequently experienced in early adulthood contributed to not finding successful medical management  (Johnson 2015). However, those who became pregnant reported finding a personally acceptable level of pain (Johnson 2015). Stigma and isolation are common. Only 1 in 4 women report feeling comfortable discussing the condition with women friends (Nguyen/MacLehose 2012).  They also report an increase in feelings of invalidation and isolation when they have co-existing pain disorders (Nguyen/Ecklund  2012).

 

  

The vulva is the external female genitalia. It includes the mons pubis, labia majora, labia minora, prepuce or clitoral hood, clitoris, and vulvar vestibule. The vulva is the center of a woman’s sexual response.  The anterior and posterior boundaries of the vulva extend from the mons pubis to the anus, respectively. Its lateral boundaries lie at the genito-crural folds. The mons pubis is comprised of a fat pad at the anterior of the vulva, which is covered in pubic hair.  The labia majora are derived embryologically from labioscrotal swellings. They fuse posteriorly and attach anteriorly to the mons pubis. The labia mi-nora, hairless folds of skin embryologically derived from urethral folds, lie within the labia majora. The labia minora fuse anteriorly, forming the prepuce (hood) of the clitoris, and extend posteriorly to either side of the vaginal opening. They fuse posteriorly at the vulvar vestibule, creating a fold of skin called the posterior fourchette. The mons pubis, perineum and labia are derived from the embryonic ectoderm. Vulvar skin is a keratinized, stratified, squamous epithelial structure that contains sebaceous glands and sweat glands. The keratin thickness of vulvar skin decreases progressively from the labia majora, over the clitoris to the labia minora. The vulvar vestibule extends from the frenulum of the clitoris anteriorly to the fourchette posteriorly. Hart’s line marks the juncture of nonkeratinized epithelium of the vestibule and the keratinized epithelium of the inner surface of the labia minora. The vulvar vestibule, derived from the urogenital sinus endoderm, contains the major vestibular glands (Bartholin’s and Skene’s) and the minor vestibular glands. The vestibular glands secrete mucous during sexual arousal and orgasm. The clitoris is located under the prepuce and is embryologically derived from the genital tubercle. It is formed of erectile corpora cavernosa tissue, which becomes engorged with blood during sexual stimulation (Farage, 2006; Krantz, 1977; Woodruff, 1985).

 

  

The vulva is innervated by the anterior labial branches of the (A) ilioinguinal nerve (L1); (B) genitofemoral nerve (L1-2); and (C, D) branches of the pudendal nerve (S2-4). Near the medial aspect of the ischial tuberosity, the pudendal nerve divides into 3 branches: (C) the dorsal nerve of the clitoris (shown deeper as dashed lines in muscles of the urogenital diaphragm), (D) the perineal nerve, which innervates the labia majora and perinuem, and (E) the inferior rectal nerve, which innervates the perianal area. The pudendal nerve also innervates the external anal sphincter and deep muscles of the urogenital triangle (Peng 2009). For a thorough review of the neurobiology of the urogenital tract, see Wesselmann, 1997.

 

  

The pelvic floor muscles are divided into 3 categories. The superficial pelvic floor muscles (bulbocavernosus or bulbospongiosus, ischiocavernosus, superficial transverse perineal/perineus muscle) are collectively known as the urogenital diaphragm. The function of the urogenital diaphragm muscles includes a role in sexual function, e.g., clitoral engorgement, vaginal closure, reflexive response to enhance sexual pleasure, and facilitating closure of the urethra and anus for continence. The middle layer is comprised of the deep transverse perineal muscle and sphincter urethra. The deep pelvic floor muscles, sometimes called the anal triangle, include the levator ani (pubococcygeus, iliococcygeus, and puborectalis), and coccygeus.  Other associated pelvic and hip muscles include the piriformis, obturator internus muscles, and gluteus maximus. The perineal body is the central tendon and attachment site for the superficial, middle, and deep pelvic floor muscles.

The internal pudendal artery, vein and nerve, which pass through Alcock’s canal, provide neurovascular function to the pelvic floor musculature.  Alcock’s canal is comprised of fascia or connective tissue from the obturator internus.  Although the pudendal nerve is known to innervate the levator ani muscles there have been more recent studies describing innervation by the levator ani nerve and direct nerve roots S3 and/or S4 (Barber 2002, Grigorescu 2008). Specifically, the pubococcygeus muscle is innervated by the levator ani nerve S3-5 and the perineal branch of the pudendal nerve S3-4. The iliococcygeus is innervated by the levator ani nerve S3-4 and the puborectalis is innervated by the inferior rectal branches of the pudendal nerve S2-S4.  The coccygeus is innervated by direct nerve roots S3-4. The function of the deep pelvic floor muscles includes: supporting the abdominal viscera or organs, providing pelvic and spinal stability, assisting in respiration, and providing sphincteric closure for bowel and bladder function. They also play a role in sexual function. (For a thorough review of the anatomy and physiology of the pelvic floor, see Herschorn 2004.)

 

  

The current classification differentiates: (i) vulvar pain due to a known cause vs. (ii) idiopathic chronic vulvar pain, i.e., vulvodynia.

 

  

Pain is first classified by location , i.e., generalized (several areas of the vulva), localized (a specific area of the vulva) or mixed; secondly, it is classified by provocation (provoked, spontaneous or mixed). It is also described by onset, either primary or secondary, and temporal pattern (intermittent, persistent, constant, immediate, or delayed). The two most common forms of vulvodynia are: (i) Generalized Vulvodynia and (ii) Provoked Vestibulodynia (formerly Vulvar Vestibulitis Syndrome).  It should be noted that women may have both a specific disorder (e.g., lichen sclerosus) and vulvodynia.

* See Slide 19 for potential associated factors.

 

  

Since 1975, many terms have been used to describe the two most common vulvodynia subtypes, causing confusion among the medical, scientific and patient communities.  

 

 

The pathophysiology of Vulvodynia remains inconclusive. (See Vulvodynia Pathophysiology References 1-50.) However, research to date supports the theory that multiple mechanisms predispose, trigger and perpetuate symptoms.

  • Co-morbidities:  painful bladder syndrome, fibromyalgia, irritable bowel syndrome, temporomandibular disorder are significantly associated with Vulvodynia.

  • Genetics: Some women with Vulvodynia have a genetic predisposition that (i) increases the risk of candidiasis or other infections, (ii) prolongs inflammatory responses or (iii) affects their response to oral contraceptive pills. 

  • Hormonal factors: In some women the use of combined hormonal contraceptives has been associated with an increased risk of Vulvodynia. 

  • Inflammation: Based on either histological, immunological or biochemical studies, inflammation has been associated with Vulvodynia. There is an increase in the number of mast cells and degranulated mast cells.

  • Musculoskeletal: Pelvic floor overactivity is frequent.

  • Neurologic mechanisms: Higher sensitivity to stimulation in non-genital areas is seen. Brain imaging studies depict function changes. 

  • Neuroproliferation: Increase in the density of nerve endings in the vestibule, i.e., nociceptors with increased density of the vanilloid receptor VR1. This leads to increased sensitivity. 

  • Psychosocial factors: Anxiety, depression, childhood victimization, posttraumatic stress, mood or anxiety disorder

  • Structural defects: There are reports that repair of pelvic floor prolapse is associated with the resolution of vulvodynia. 

 

 

Our understanding of the pathophysiological mechanisms of vulvodynia is in its infancy. This diagram compares the mechanisms of normal pain transmission to the proposed pathophysiologic transmission of pain in women with vulvodynia. It is likely that different mechanisms, influenced by several predisposing, triggering and maintaining factors, as well as genetic and environmental factors, will be identified. 

 

 

One possible pathophysiological mechanism of Vestibulodynia is neuroproliferation. A special nerve fiber staining, PGP 9.5, was used to depict small nerve fibers in patients with Vestibulodynia and women without Vestibulodynia undergoing vestibular biopsy for other conditions. Subepithelial and intraepithelial nerve fibers were detected only in patients with Vestibulodynia. The fibers penetrated the basal membrane and continued vertically for more than half the distance to the epithelial surface. Branching of the nerve fibers within the epithelium was rarely seen (Bornstein 1997, Bornstein 2008).

 

 

In Vestibulodynia there is frequently an increase in mast cell number and activity. Here, mast cells, stained by Giemsa, show degranulation as evidenced by the extracellular red granules, in a X600 microscopic field. The discharged granules contain Tryptase, Histamine, Serotonin, Histamine, Bradykinin, Heparanase, Nerve Growth Factor, etc. Some of these enzymes may participate in the pathogenesis of Vestibulodynia (Bornstein 2004).

 

 

Preliminary findings of research on factors associated with the risk of developing vulvodynia indicate that there may be multiple risk factors involved, but larger studies are needed to confirm these findings. Multiple studies suggest that vulvodynia patients experience more frequent vaginal infections, however, in most cases, prior vaginal infections were either self-reported or unconfirmed by the treating clinician. Research demonstrates that patients and clinicians are poor at accurately diagnosing vaginal infections (Ferris 1996, Ferris 2002, Ledger 2004, Schwiertz 2006). The only population-based case-control study to date, which compared the frequency of self-reported urogenital infections before the onset of vulvar pain, demonstrated that a history of genital warts (OR 3.4), trichomoniasis (OR 5.7), urinary tract infection (OR 2.0) or yeast infection (OR 2.1) was associated with increased risk of vulvodynia. The researchers also found that women with multiple infections prior to the onset of vulvar pain were at highest risk; a combination of urinary tract infection and STIs was associated with a 10-fold higher risk (Nguyen 2009). Recent pathophysiological studies have demonstrated a relationship between vulvodynia and Candida albicans (Babula 2004, Foster 2007, Ramirez De Knott 2005, Farmer 2011). 

Research to date appears to implicate oral contraceptive (OC) use in the development and/or maintenance of vulvodynia in some subgroups. Some clinicians propose that the use of OCs, particularly at an early age, down-regulates estrogen receptors in the vulvovaginal tissue, causing the vestibular epithelium to become thin and fragile. In a study of women using Yasmin, Battaglia (2012) found decreased labial thickness, introital area, frequency of intercourse and orgasm during intercourse, as well as increased pain with intercourse and pulsatility index of the dorsal clitoral and posterior labial arteries. In another study, quantitative sensory testing of the vestibular mucosa in healthy women revealed significantly lower mechanical pain thresholds in the OC group, with the most sensitivity in the posterior vestibule. The investigators concluded that OCs may induce increased sensitivity in the vestibular mucosa in healthy women, possibly contributing to the development of vulvodynia (Bohm-Starke 2004). Heddini (2012) found that Provoked Vestibulodynia patients carrying a polymorphism in the guanosine triphosphate cyclohydrolase (GCH1) gene and using OCs had higher pain sensitivity compared to non-carriers. Several studies have demonstrated increased risk in this patient population (Sjoberg 1997, Greenstein 2007, Bazin 1994, Bouchard 2002), although a population-based study did not (Harlow 2008).  

Other risk factors reported in the literature include a history of allergies (Harlow 2009); vulvar dermatoses (Coombs 2011); autoimmune disease (Driul 2011) and an altered immuno-inflammatory response (Breshears 2011); early age of menarche (Harlow 2001); dysmenorrhea (Granot 2004); difficulty or severe pain with first tampon use (Harlow 2003, Landry 2009, Legocki 2011); early age of first intercourse (Bazin 1994, Berglund 2002); pain with first intercourse (Legocki 2011); pain with/after sex (Reed 2012); nulliparity (Edgardh 2007); childhood nocturnal enuresis (Greenstein 2005); urinary burning (Reed 2012); nocturnal urination, pain with wiping, and bike riding (Legocki 2011); genetic variability (Babula 2008, Foster 2004, Gerber 2003, Jeremias 2000, Lev-Sagie 2009) and altered gene expression, particularly in genes implicated in osteoarthritis (Breshears 2011) and with an altered immuno-inflammatory response (Bornstein 2004, Bornstein 2008, Foster 1997, Foster 2007, Gerber 2002, Harlow 2009, Lev-Sagie 2009); and chronic pain in other areas of the body (Falik-Zaccai 2011, Arnold 2006, Heddini 2012). (See Section 6 Comorbidity references.)

Although one study supports some degree of association (Harlow 2005), several studies have refuted the notion that prior sexual and/or physical abuse is a risk factor for vulvodynia (Dalton 2002, Plante 2008, Edwards 1997, Reed 2000). Khandker (2011) is the only population-based epidemiological study to demonstrate antecedent depression and anxiety as risk factors for vulvodynia. Plante (2008) demonstrated that women with vulvodynia reported more adverse life experiences.

See Bohm-Starke 2010 for additional information.

 

 

According to the ISSVD (Bornstein 2016), known causes of chronic vulvar pain are: (1) infectious, (2) inflammatory, (3) neoplastic, (4) traumatic, (5) iatrogenic, (6) hormonal deficiencies,  or (7) neurologic. If the cause is unknown, it is classified as vulvodynia. Conditions falling into the first seven categories must be ruled out prior to making a diagnosis of vulvodynia. Examples of some of these prevalent conditions follow, with references to journal articles that provide information on diagnosis and treatment. (This is beyond the scope of the current program.)

 

 

The image on the left is a vaginal smear identifying Candida albicans, using a gram stain technique. In-office diagnosis can be made with microscopy, using a potassium hydroxide prep, and vaginal culture can be used for speciation and sensitivity. Candida albicans is a component of the normal flora in many women. Under certain conditions, such as a hormone imbalance, antibiotic treatment, or transient localized immune suppression, C. albicans can multiply, resulting in a symptomatic condition known as vulvovaginal candidiasis. Recent studies have implicated recurrent or chronic vulvovaginal candidiasis as a causative factor in vulvodynia. 

It should be noted that the microbiome of the vagina is very complex and many species of bacteria, which may be considered pathogens in other parts of the body, are not pathogens in the vagina. Bacterial species such as Group Beta Strep, Klebsiella, and e. coli are common in the vagina and should not be treated.  

 

 

The image on the left is a phase contrast wet mount micrograph of a vaginal discharge revealing the presence of Trichomonas vaginalis protozoa. Trichomoniasis is a sexually transmitted infection that causes itching, irritation and abnormal discharge.

As seen on the right, genital herpes simplex (virus 1 or 2) infection typically presents as one or more blisters on or around the genitals or rectum. The blisters break, leaving tender ulcers that may take two to four weeks to heal the first time they occur. Frequently, genital herpes presents with more subtle signs, such as a small fissure or break in the skin. Viral shedding can also occur in the absence of visible manifestation.

Lichen sclerosus (LS) is a chronic inflammatory condition of the vulva, most likely of autoimmune etiology. Both photos show cases of LS, but the photo on the left shows a severe case with a whitish color, itching, and fragile skin that may bruise or tear with contact or sexual intercourse. Diagnosis should be confirmed with vulvar skin biopsy evaluated by a dermatopathologist prior to initiating treatment with ultra-potent topical corticosteroids.

 

 

Erosive lichen planus (LP) is another autoimmune skin disorder that can affect the vulva.  As seen in these photos, lichen planus typically presents with white irregular lines and deep red areas of painful erosions.

 

 

The photo on the left shows nondescript redness in a woman who has an irritant contact dermatitis from using a harsh soap. Contact dermatitis is a rash resulting from the skin’s reaction to an external substance, e.g., ointments, soaps, detergents, dyes or sanitary pads. The rash may occur suddenly with blisters, itching and weeping or it may be of slower onset with redness, burning and some swelling. There are two types of contact dermatitis – irritant and allergic.  Irritant dermatitis is the most common type causing burning, rawness and/or irritation.  Allergic dermatitis may be mild, with simply minor redness, swelling and itching, or severe, with blistering, bright red swelling and severe discomfort.     

The primary symptom of lichen simplex chronicus (aka eczema, atopic dermatitis, neurodermatitis) is itching. Pain and skin abnormalities result from rubbing or scratching, as can be seen from the rubbed and thickened skin in this photo. Lichen simplex chronicus frequently starts because of chronic inflammation from chronic/recurrent candidiasis or recurrent exposure to an irritant and/or allergen, or less commonly vulvar intraepithelial neoplasia (VIN). This chronic inflammation causes an itch-scratch cycle that leads to lichen simplex chronicus. Treatment consists of treating the infectious organism or removal of the allergen or irritant exposure. Application of ice, and an antihistamine or tricyclic antidepressant, are then used to stop the pruritus to break the itch-scratch cycle. Lastly, a potent topical corticosteroid is used to reduce the inflammation. 

These photos show vulvas with squamous cell carcinoma (SCC) on a background of LS. SCC can develop in 3-5% of women with LS. An additional cause of vulvar SCC is HPV infection, which can cause vulvar intraepithelial neoplasia and then progress to SCC. Additionally, melanoma and Paget disease can occur on the vulva. Therefore, in any patient with persistent ulceration, a mass or irregular pigmented lesion, the clinician should perform a vulvar biopsy to rule out malignancy. 

 

 

 

 

The MRI on the left shows a Tarlov cyst, a CSF-filled sac located in the spinal canal at the S1-S4 region of the spinal cord. Patients with Tarlov cysts are usually asymptomatic, but some do experience radiating pelvic and urogenital pain, persistent genital arousal disorder (PGAD), sexual dysfunction and bladder dysfunction, among other symptoms.

The image on the right shows a labral hip tear, which can refer pain to the urogenital region.

 

 

More than 130 million women across the world have undergone Female Genital Cutting (FGC) and in some countries prevalence of FGC is greater than 85% (UNICEF 2014).

Perineal trauma from a poorly healed or poorly repaired laceration or episiotomy may cause chronic vulvar pain or recurrent tearing (and pain) during intercourse. A recent review showed that 12.8% of women experience chronic vulvar pain at least five months after episiotomy (Turmo 2015).

Lastly, straddle injuries (most commonly from bicycles or falls from climbing) or injuries to the pelvis from motor vehicle accidents are uncommonly the cause of persistent vulvar pain.  

 

 

It has been recognized for decades that the tissues of the vulva and vagina are both responsive and dependent on sex steroids (hormones) for proper health and function. These sex steroids exert their effects through the nuclear receptors of estrogen, progesterone, androgen and glucocorticoid . The hormone receptors are very abundant in the epithelium of the outer vulva, endothelium of the vestibule, and mesothelium of the vagina. In addition, these hormone receptors are also found in high concentration in the deeper tissues of the vulva and vagina, including the glands and connective tissue, and adjacent to blood vessels and nerves. The hormones bind to the hormone receptors, which then leads to transcription and production of proteins that are essential for genital health and normal sexual function. Conversely, a deficiency in the sex steroids leads to dysfunction and frequently dyspareunia. It has been very well documented that a deficiency in circulating estrogen leads to anatomic and physiologic changes in the vagina. Anatomic changes include reduced collagen density and hyalinization, decreased elastin, thinning of the epithelium, altered appearance and function of smooth muscle cells, increased density of connective tissue, and fewer blood vessels. The labia minora thin and regress, the vestibule retracts, and the hymenal carunculae involute and lose elasticity. The urethral meatus appears prominent relative to the vestibule and becomes vulnerable to physical irritation and trauma. Physiologic changes result in reduced vaginal blood flow, diminished lubrication, decreased flexibility and elasticity of the vaginal vault, and increased vaginal pH. Furthermore, decreases in vaginal tissue strength and increased friability may predispose to epithelial damage with penetrative sexual activity, leading to pain, burning, tearing, irritation, and post-coital bleeding. Epithelial thinning with decreased glycogenated superficial cells leads to changes in vaginal flora and loss of lactobacilli, increased pH, and a change in the microbiome. More recently, it has become apparent that deficiency in circulating free testosterone also adversely affects the tissues of the vulva and vagina. Decreased levels of androgens are associated with decreased mucinification, decreased nerve fiber density, and decreased vasodilatation.

 

 

As seen in these photographs, women who receive adjuvant endocrine therapy after the diagnosis of breast cancer (with an aromatase inhibitor or Tamoxifen), have a significant increase in dyspareunia (Baumgart 2013).

Prophylactic oophorectomy in women with BRCA mutations also increases the rate of dyspareunia (Finch 2011).

Sixty-seven percent of women who receive pelvic radiation therapy for anogenital malignancies develop dyspareunia (Stinesen 2015).

Repair of pelvic organ prolapse with synthetic vaginal mesh may have significant complications, including mesh contraction; mesh erosion into the vagina, bladder, and bowel; and dyspareunia. A meta-analysis of 71 papers showed that the overall rate of chronic dyspareunia after mesh placement is 9.1% (Abed 2011).

After visible and/or neurologic causes of vulvar pain are identified and treated, one moves on to evaluate the patient for vulvodynia. Hyperalgesia and allodynia are present, with or without the presence of erythema. Although women with vulvodynia describe their pain in a variety of ways, e.g., stabbing, aching, raw, searing, sharp, throbbing, knife-like, etc., burning is most commonly reported. If the pain is localized to the vulvar vestibule and provoked, the diagnosis is likely to be Provoked Vestibulodynia (PVD). PVD is further categorized as primary or secondary. PVD is the most common subtype affecting 80 percent of women with chronic vulvar pain symptoms (Harlow 2003). If the pain is generalized to multiple areas of the vulva and spontaneous, but exacerbated by touch/pressure, the diagnosis is likely Generalized Vulvodynia. Twenty percent of women suffer from this subtype or a mixture of both.

* The two subtypes can coexist (Reed 2003, Edwards 2004).

 

 

Based on data from an NIH-funded population-based study, the above four questions have been found to be highly predictive of an office-based diagnosis of vulvodynia (Harlow 2009). These questions were validated against clinical examination with 80% specificity and 95% sensitivity. They should be included on screening forms to help health care practitioners identify women and adolescents who may be suffering from the condition.

 

 

For more than a decade, gynecologists, dermatologists, vulvar pain specialists, and researchers have used the 2003 ISSVD terminology as a guide to diagnosing vulvar pain.This terminology evolved over years of discussion on the nature of idiopathic vulvar pain, especially that occurring during sexual activity and vaginal penetration. The 2003 terminology divided vulvar pain into two overarching categories: vulvar pain related to a specific disorder, and vulvodynia, defined specifically as “vulvar discomfort, most often described as burning pain, occurring in the absence of relevant visible findings or a specific, clinically identifiable, neurologic disorder.” Therefore, the term vulvodynia was reserved for those cases in which the pain could not be attributed to an identifiable “visible” cause.

Since 2003, the category of identifiable causes of vulvar pain has evolved substantially, as have the potential factors associated with vulvodynia. These developments are based on the results of numerous studies examining a wide range of possible etiological factors (e.g., inflammatory, genetic, musculoskeletal, neurosensory, neuropathic) and treatment avenues (e.g., oral medication, pelvic floor physical therapy, surgical intervention, psychological intervention). These studies have also led to the conclusion that vulvodynia is likely not one disease but a constellation of symptoms of several (sometimes overlapping) disease processes that benefits most from a range of treatments based on individual presentation. These studies have widened the scope of etiological considerations and have resulted in the need to update the description and nomenclature of persistent vulvar pain. In addition, several important pain characteristics of vulvodynia have been introduced (e.g., primary and secondary status; intermittent and constant pain pattern).  

 

 

As shown on the left, most women with Generalized Vulvodynia report spontaneous pain in multiple areas of the vulva. Pain tends to be constant, but may be intermittent in some women. Although symptoms are spontaneous, they tend to worsen with provocation. Periods of unexplained pain relief and/or flares can occur. Erythema may or may not be present. This subtype affects 20 percent of those reporting chronic vulvar pain symptoms (Harlow 2003).

 As shown on the right, women with Provoked Vestibulodynia report provoked pain only within the vulvar vestibule. Erythema may co-occur. This subtype affects 80 percent of those with vulvar pain (Harlow 2003).

 A subset of women report spontaneous widespread vulvar pain, as well as provoked pain localized to the vestibule. The above subtypes may coexist in some women (Reed 2003, Edwards 2004).    

 

 

Women may present with marked introital erythema, as seen in patient #1, or the tissue may appear relatively normal, as seen in patient #3. Although patient #3 presented with minimal erythema, she had severe pain, which prevented her from engaging in sexual intercourse or inserting a tampon. Recent studies have also shown that pain severity and subsurface inflammation do not consistently correlate with the severity of erythema observed. The relevance of this criterion is disputed. 

 

 

Current guidelines recommend that a cotton-swab test be performed (Haefner 2005). The 11 sites shown on this diagram should be tested for allodynia and hypo- or hyperalgesia by applying gentle pressure with a dry cotton-swab (just enough to slightly indent the skin). If symptoms are provoked and localized to the vestibule, a more thorough evaluation of the vestibule is warranted and is described in the next slide.

 

 

Sites to be tested within the vulvar vestibule can be visualized using a clock face (1-12 o’clock) with one vertical and one perpendicular (black) line through the center of the vaginal opening. The 2 and 5 o’clock positions are equidistant to both lines, as are the 7 and 10 o’clock positions. The anterior vestibular sites (2, 10 and 12) are typically assessed first, followed by the posterior sites (5, 6 and 7). Again, gentle pressure is applied to each of these sites and women are asked to rate the pain severity and describe the character of the pain they experience (Zolnoun 2012).  

 

 

NIH-funded foundational work at the University of North Carolina at Chapel Hill is currently ongoing to refine a vulvovaginal neurosensory examination (described in this slide). Current prospective patient-reported outcomes studies are underway to delineate the exam components that are clinically relevant and predictive of treatment response (PI Zolnoun, NIH Grant 5K23HD053631, description available at: https://projectreporter.nih.gov/project_info_results.cfm?aid=7927135&icde=0). 

The muscle assessment begins with the examiner’s right index finger (bent approximately 30-60 degrees) palpating the patient’s right mid-pubic rami, which is the bony landmark for identifying the mid-segment (belly) of puborectalis muscle. After confirming the mid-position placement of the index finger, the examiner palpates the puborectalis muscle, which is immediately adjacent/behind the pubic rami. Then, the examiner rotates the index finger downwards (approximate length of 1-1.5 cm) parallel to the length of puborectalis, until the transition point/insertion to the superficial muscles (perineal muscle complex) is palpated. Using the left index finger, the examiner assesses the left puborectalis as described above and seen in this slide. The perineal muscle complex, which is immediately beneath the 6 o’clock mucosal position, is palpated last. These muscle sites are adjacent to the respective lower vestibular mucosal sites (5, 6, and 7). Women are asked to describe the pain character and rate the pain severity they experience (Zolnoun 2012).

 

 

Women with vulvodynia commonly report suffering from comorbid pain disorders, mood/sleep alteration and sexual impairment. It is vital to assess all of the factors that are contributing to a woman’s current pain state in order to delineate the most appropriate components of an individualized, multidisciplinary treatment regimen.

In a 2008 literature review, Desrochers critically examined studies on the psychosexual aspects of vulvodynia and concluded that, despite the presence of methodological limitations, some findings were consistently replicated. Overall, women with vulvodynia demonstrated impaired sexual functioning, including lower levels of sexual desire, arousal, and frequency of intercourse. Additionally, questionnaires revealed that anxiety, fear of pain, hypervigilence and depression were more prevalent among these women. Desrochers concluded that more rigorous studies are needed to establish whether psychosexual variables exacerbate and/or maintain vulvodynia.

A growing body of literature documents the association between vulvodynia and other chronic pain conditions. Warren (2008) proposed that vulvodynia may be a referred pain of interstitial cystitis in many cases. Several authors have proposed that both IC and vulvodynia are syndromes of the urogenital sinus-derived epithelium (McCormack 1990, Burrows 2008). Peters (2008) speculated that the conditions may be linked by common pelvic floor muscle dysfunction. Others have proposed that a common pathway may stimulate a single disease process (Kennedy 2007), or that in some women, IC and vulvodynia may be the same disease (Peters 2008).

Recently, researchers have explored the relationship between vulvodynia and orofacial pain, specifically temporomandibular disorders. Zolnoun (2008) speculated that a subset of vulvodynia patients may suffer from a widespread musculoskeletal pain disorder influenced more by genetic makeup and central nervous system dysfunction than by an inflammatory process in the vulva.

Kennedy (2007) proposed that: (i) IBS may predispose women to certain vulvar conditions (perhaps by the irritant nature of diarrhea, for example), (ii) treatment for vulvar conditions may lead to bowel symptoms, or (iii) both conditions may represent a “pelvic floor pain disorder.” 

When studying the relationship between fibromyalgia and vulvodynia, Pukall (2005, 2006) proposed that the mechanisms involved in vulvodynia may be genital-specific in some women and possibly centrally mediated in others. Whether the generalized sensitivity or vulvar pain occurs first is unknown. For example, an untreated vulvar irritation could lead to central changes in sensory processing in genetically predisposed women, resulting in altered central pain processing and a widespread increase in sensitivity. On the other hand, women with vulvodynia may be more sensitive to pain in general and develop vulvar pain through a locally occurring event, such as a vulvar injury.  

This proposed diagnostic algorithm for vestibulodynia has been adapted from King M, Rubin R, Goldstein A. Current Uses of Surgery for the Treatment of Genital Pain. Current Sexual Health Reports. 2014, Oct 3. Volume 6, Issue 4, pp. 252-8. Shown on this slide are two potential causes of pain that affect the entire vestibule. King et al. postulate that if the entire vestibular endoderm (mucosa) is painful, it is likely that there is pathologic process occurring in this tissue. The next three slides show additional causes of vestibulodynia with different underlying pathological mechanisms. Subtle differences in the history (HX) and physical examination (PE) may help to differentiate between potential causes of vestibulodynia, which may lead to disease-specific treatments.

 

 

This proposed diagnostic algorithm for vestibulodynia has been adapted from King M, Rubin R, Goldstein A. Current Uses of Surgery for the Treatment of Genital Pain. Current Sexual Health Reports. 2014, Oct 3. Volume 6, Issue 4, pp. 252-8. 

 

 

This proposed diagnostic algorithm for vestibulodynia has been adapted from King M, Rubin R, Goldstein A. Current Uses of Surgery for the Treatment of Genital Pain. Current Sexual Health Reports. 2014, Oct 3. Volume 6, Issue 4, pp. 252-8.

 

 

This proposed diagnostic algorithm for vestibulodynia has been adapted from King M, Rubin R, Goldstein A. Current Uses of Surgery for the Treatment of Genital Pain. Current Sexual Health Reports. 2014, Oct 3. Volume 6, Issue 4, pp. 252-8. In this slide are the potential causes of pain in the posterior vestibule or pain that extends beyond the vestibule. King et al postulate that if only part of the vestibular endoderm is painful, it is not likely that there is an intrinsic pathologic process occurring within the vestibular tissue. More likely, pain affecting only part of the vestibule is the result of a pathologic process extrinsic to the vestibule such as overactive pelvic floor muscle dysfunction (aka vaginismus or levator ani syndrome). Tenderness that extends outside of the vestibule is likely pudendal neuralgia. 

 

 

 

 

 

 

*Patient recommendations for vulvar self-care can be viewed at: http://www.nva.org/tips.

^Detailed dosing and side effect information/charts for oral (and topical) medications used to treat vulvodynia are contained in The Vulvodynia Guideline, which can be viewed/downloaded at: www.nva.org/haefner.

** In the medical literature, only two randomized controlled trials have evaluated the efficacy of oral tricyclic antidepressants. Neither randomized controlled trial found positive results, i.e., the treatment provided only minimal relief of vulvar pain. These studies, however, included women with localized and generalized vulvodynia, as well as women with provoked and unprovoked vulvodynia, so treatment efficacy for specific subgroups is unknown.

Despite their widespread use, even less efficacy data is available on anticonvulsants than on tricyclic antidepressants, with only three retrospective case series conducted to date. Even though these studies reported positive findings, there were no control groups. The first randomized controlled trial evaluating gabapentin for treatment of vulvodynia is ongoing (Brown CS, Foster DC, Bachmann GA. A Controlled Trial of Gabapentin in Vulvodynia: Biological Correlates of Response). See the following website for more information, https://clinicaltrials.gov/show/NCT01301001.

*Nifedipine did not exceed placebo among women with vulvodynia in a double-blind study (107). Other topicals that are not useful include corticosteroids, progesterone, and antifungals (108).

 

 

 

 

 

 

Landry et al. provide a thorough review of surgical treatment studies (28).

This is an image of the vulva three months post-vestibulectomy and vaginal advancement. In this type of surgery, the vagina is pulled and sutured to the perineal skin, halfway between the vulvar introitus and the anus so that the sensitive mucosa-skin junction will not be in the introitus itself (128).

 

 

  

 

 

 

 

 

^Alternative Therapies:

Hypnotherapy:  Limited findings for hypnotherapy noted significant decrease in pain associated with intercourse and increase in sexual satisfaction in nine women with vestibulodynia (129, 130).

Acupuncture:  Limited reports of improvement in vulvar pain and dyspareunia, including one randomized study comparing vulvodynia  patients to waitlist controls (133, 134).

 

 

PainTracker is an evidence-based tool available to individual health care providers for use to track key domains and treatment outcome over time. A quick overview of program, interface and questionnaire can be viewed at: http://www.nva.org/tools. Request login information to review the web interface from: https://paintracker.cirg.washington.edu/demo/users/login. 

 *The FSFI can be viewed/downloaded here: www.nva.org/tools.

^ Instruments available through NIH PROMIS can be viewed here: https://www.assessmentcenter.net/documents/InstrumentLibrary.pdf.

^^A recent study found smartphone tracking system promoted excellent compliance with weekly tracking (135). Examples include: WebMD Pain Coach, My Pain Diary , Chronic Pain Tracker and Manage My Pain.

 

 

 

 

 

 

 

 

Begin the post-test (Free activity)